Cargando…

Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1

Bupivacaine is an amide type long acting local anesthetic used for epidural anesthesia and nerve blockade in patients. Use of bupivacaine is associated with severe cytotoxicity and apoptosis along with inhibition of cell growth and proliferation. Although inhibition of Erk, Akt, and AMPK seemingly a...

Descripción completa

Detalles Bibliográficos
Autores principales: Beigh, Mushtaq Ahmad, Showkat, Mehvish, Bashir, Basharat, Bashir, Asma, Hussain, Mahboob ul, Andrabi, Khurshid Iqbal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925553/
https://www.ncbi.nlm.nih.gov/pubmed/24605337
http://dx.doi.org/10.1155/2014/831845
_version_ 1782303875879927808
author Beigh, Mushtaq Ahmad
Showkat, Mehvish
Bashir, Basharat
Bashir, Asma
Hussain, Mahboob ul
Andrabi, Khurshid Iqbal
author_facet Beigh, Mushtaq Ahmad
Showkat, Mehvish
Bashir, Basharat
Bashir, Asma
Hussain, Mahboob ul
Andrabi, Khurshid Iqbal
author_sort Beigh, Mushtaq Ahmad
collection PubMed
description Bupivacaine is an amide type long acting local anesthetic used for epidural anesthesia and nerve blockade in patients. Use of bupivacaine is associated with severe cytotoxicity and apoptosis along with inhibition of cell growth and proliferation. Although inhibition of Erk, Akt, and AMPK seemingly appears to mediate some of the bupivacaine effects, potential downstream targets that mediate its effect remain unknown. S6 kinase 1 is a common downstream effector of several growth regulatory pathways involved in cell growth and proliferation known to be affected by bupivacaine. We have accordingly attempted to relate the growth inhibitory effects of bupivacaine with the status of S6K1 activity and we present evidence that decrease in cell growth and proliferation by bupivacaine is mediated through inactivation of S6 kinase 1 in a concentration and time dependent manner. We also show that ectopic expression of constitutively active S6 kinase 1 imparts substantial protection from bupivacaine induced cytotoxicity. Inactivation of S6K1 though associated with loss of putative mTOR mediated phosphorylation did not correspond with loss of similar phosphorylations in 4EBP1 indicating that S6K1 inhibition was not mediated through inactivation of mTORC1 signaling pathway or its down regulation.
format Online
Article
Text
id pubmed-3925553
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-39255532014-03-06 Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1 Beigh, Mushtaq Ahmad Showkat, Mehvish Bashir, Basharat Bashir, Asma Hussain, Mahboob ul Andrabi, Khurshid Iqbal Biomed Res Int Research Article Bupivacaine is an amide type long acting local anesthetic used for epidural anesthesia and nerve blockade in patients. Use of bupivacaine is associated with severe cytotoxicity and apoptosis along with inhibition of cell growth and proliferation. Although inhibition of Erk, Akt, and AMPK seemingly appears to mediate some of the bupivacaine effects, potential downstream targets that mediate its effect remain unknown. S6 kinase 1 is a common downstream effector of several growth regulatory pathways involved in cell growth and proliferation known to be affected by bupivacaine. We have accordingly attempted to relate the growth inhibitory effects of bupivacaine with the status of S6K1 activity and we present evidence that decrease in cell growth and proliferation by bupivacaine is mediated through inactivation of S6 kinase 1 in a concentration and time dependent manner. We also show that ectopic expression of constitutively active S6 kinase 1 imparts substantial protection from bupivacaine induced cytotoxicity. Inactivation of S6K1 though associated with loss of putative mTOR mediated phosphorylation did not correspond with loss of similar phosphorylations in 4EBP1 indicating that S6K1 inhibition was not mediated through inactivation of mTORC1 signaling pathway or its down regulation. Hindawi Publishing Corporation 2014 2014-01-29 /pmc/articles/PMC3925553/ /pubmed/24605337 http://dx.doi.org/10.1155/2014/831845 Text en Copyright © 2014 Mushtaq Ahmad Beigh et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Beigh, Mushtaq Ahmad
Showkat, Mehvish
Bashir, Basharat
Bashir, Asma
Hussain, Mahboob ul
Andrabi, Khurshid Iqbal
Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1
title Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1
title_full Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1
title_fullStr Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1
title_full_unstemmed Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1
title_short Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1
title_sort growth inhibition by bupivacaine is associated with inactivation of ribosomal protein s6 kinase 1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925553/
https://www.ncbi.nlm.nih.gov/pubmed/24605337
http://dx.doi.org/10.1155/2014/831845
work_keys_str_mv AT beighmushtaqahmad growthinhibitionbybupivacaineisassociatedwithinactivationofribosomalproteins6kinase1
AT showkatmehvish growthinhibitionbybupivacaineisassociatedwithinactivationofribosomalproteins6kinase1
AT bashirbasharat growthinhibitionbybupivacaineisassociatedwithinactivationofribosomalproteins6kinase1
AT bashirasma growthinhibitionbybupivacaineisassociatedwithinactivationofribosomalproteins6kinase1
AT hussainmahboobul growthinhibitionbybupivacaineisassociatedwithinactivationofribosomalproteins6kinase1
AT andrabikhurshidiqbal growthinhibitionbybupivacaineisassociatedwithinactivationofribosomalproteins6kinase1